tert-butyl (3S)-3-({[(2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate | 1174021-11-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl (3S)-3-({[(2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate
• 英文别名: (S)-3-[((2S,5R)-6-Hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-amino]-pyrrolidine-1-carboxylic acid tert-butyl ester；tert-butyl (3S)-3-[[(2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonyl]amino]pyrrolidine-1-carboxylate
• CAS: 1174021-11-4
• 化学式: C₁₆H₂₆N₄O₅
• 分子量: 354.406
• InChiKey: DBJGUUODMUBEKJ-TUAOUCFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (3S)-3-({[(2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate 在 吡啶 、 三氧化硫吡啶 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (2S,5R)-7-oxo-N-[(3S)-pyrrolidin-3-yl]-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]-octane-2-carboxamide
  参考文献：
  名称：

  Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®

  摘要：

  beta-Lactamase inhibitors with a bicyclic urea core and a variety of heterocyclic side chains were prepared and evaluated as potential partners for combination with imipenem to overcome class A and C beta-lactamase mediated antibiotic resistance. The piperidine analog 3 (MK-7655) inhibited both class A and C beta-lactamases in vitro. It effectively restored imipenem's activity against imipenem-resistant Pseudomonas and Klebsiella strains at clinically achievable concentrations. A combination of MK-7655 and Primaxin (R) is currently in phase II clinical trials for the treatment of Gram-negative bacterial infections. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.101
• 作为产物：
  描述：

  (2S,5R)-6-(苄氧基)-7-氧代-1,6-二氮杂双环[3.2.1]辛烷-2-羧酸 在 palladium on activated charcoal 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 tert-butyl (3S)-3-({[(2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®

  摘要：

  beta-Lactamase inhibitors with a bicyclic urea core and a variety of heterocyclic side chains were prepared and evaluated as potential partners for combination with imipenem to overcome class A and C beta-lactamase mediated antibiotic resistance. The piperidine analog 3 (MK-7655) inhibited both class A and C beta-lactamases in vitro. It effectively restored imipenem's activity against imipenem-resistant Pseudomonas and Klebsiella strains at clinically achievable concentrations. A combination of MK-7655 and Primaxin (R) is currently in phase II clinical trials for the treatment of Gram-negative bacterial infections. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.101

文献信息

• BETA-LACTAMASE INHIBITORS
  申请人：Blizzard Timothy A.

  公开号：US20110294777A1

  公开（公告）日：2011-12-01

  Substituted bicyclic beta-lactams of Formula I: (I), are β-lactamase inhibitors, wherein a, X, R 1 and R 2 are defined herein. The compounds and pharmaceutically acceptable salts thereof are useful in the treatment of bacterial infections in combination with β-lactam antibiotics. In particular, the compounds can be employed with a β-lactam antibiotics (e.g., imipenem, piperacillin, or ceftazidime) against microorganisms resistant to β-lactam antibiotics due to the presence of the β-lactamases.

  化合物I的替代双环β-内酰胺(I)是β-内酰胺酶抑制剂，其中a、X、R1和R2如此定义。该化合物及其药学上可接受的盐在与β-内酰胺类抗生素联合治疗细菌感染方面是有用的。特别地，该化合物可与β-内酰胺类抗生素（例如亚胺培南、哌拉西林或头孢他啶）一起用于对抗由β-内酰胺酶存在而对β-内酰胺类抗生素产生耐药性的微生物。
• PREPARATION OF ALKYL ESTERS OF N-PROTECTED OXO-AZACYCLOALKYLCARBOXYLIC ACIDS
  申请人：Mangion Ian

  公开号：US20120053350A1

  公开（公告）日：2012-03-01

  A process for the preparation of alkyl esters of N-protected oxo-azacycloalkylcarboxylic acids of Formula III: comprises contacting a ketosulfoxonium ylide of Formula II: with an iridium catalyst to obtain Compound III, wherein P G1 is an amine protective group; k is 0, 1, or 2; and R U , R 1 , R 2 , and R 3 are defined herein. An embodiment of the process further com rises contacting a compound of Formula I: with a sulfoxonium halide of formula (R U ) 3 S(O)Z, wherein Z is halide, in the presence of a strong base to obtain Compound II. Additional embodiments add a series of process steps leading to the synthesis of 7-oxo-1,6-diazabicyclo[3.2.1]octanes suitable for use as β-lactamase inhibitors.

  一种制备式III的N-保护氧杂环烷基羧酸烷基酯的方法：包括将式II的酮亚磺酸叶立德与铱催化剂接触以获得化合物III，其中PG1为氨基保护基；k为0、1或2；RU、R1、R2和R3在此被定义。该方法的一种实施还包括将式I的化合物与式(RU)3S(O)Z的亚磺酸卤化物接触，在强碱存在下获得化合物II。其他实施例添加了一系列的过程步骤，可导致合成适用于作为β-内酰胺酶抑制剂的7-氧代-1,6-二氮杂双环[3.2.1]辛烷。
• β-lactamase inhibitors
  申请人：Blizzard Timothy A.

  公开号：US08487093B2

  公开（公告）日：2013-07-16

  Substituted bicyclic beta-lactams of Formula I: (I), are β-lactamase inhibitors, wherein a, X, R1 and R2 are defined herein. The compounds and pharmaceutically acceptable salts thereof are useful in the treatment of bacterial infections in combination with β-lactam antibiotics. In particular, the compounds can be employed with a β-lactam antibiotics (e.g., imipenem, piperacillin, or ceftazidime) against microorganisms resistant to β-lactam antibiotics due to the presence of the β-lactamases.

  公式I中的替代双环β-内酰胺(I)是β-内酰胺酶抑制剂，其中a，X，R1和R2在此定义。所述化合物及其药学上可接受的盐可与β-内酰胺类抗生素结合治疗细菌感染。特别地，该化合物可与β-内酰胺类抗生素（例如亚胺培南、哌拉西林或头孢他啶）联合使用，以对抗由β-内酰胺酶引起的对β-内酰胺类抗生素产生耐药性的微生物。
• [EN] BETA-LACTAMASE INHIBITORS<br/>[FR] INHIBITEURS DE BÊTA-LACTAMASE
  申请人：MERCK & CO INC

  公开号：WO2009091856A3

  公开（公告）日：2009-12-03
• [EN] PREPARATION OF ALKYL ESTERS OF N-PROTECTED OXO-AZACYCLOALKYLCARBOXYLIC ACIDS<br/>[FR] PRÉPARATION D'ESTERS ALKYLIQUES D'ACIDES OXO-AZACYCLOALKYLCARBOXYLIQUES N-PROTÉGÉS
  申请人：MERCK SHARP & DOHME

  公开号：WO2010126820A3

  公开（公告）日：2011-06-09